Free hCGβ and Nongonadal Neoplasms

Bellet, Dominique; Rouas, Nathalie; Marcillac, Isabelle; Housseau, Frank; Cottu, Paul; Troalen, Frédéric; Bidart, Jean‐Michel

doi:10.1007/978-1-4613-8386-4_20

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“…Synthesis of the gonado¬ tropin subunits in rodents has been reported to take place exclusively in the anterior pituitary (Pierce & Parsons However, some findings exist on extrapituitary production and/or localization of gonadotropins, or their subunits, in the hypothalamus (Emanuele et al 1981, Hojvat et al 1982, Hostetter et al 1987, human breast tissue (Garde et al 1993), human, rat and mouse testis (Wahlström et al 1983, Hovatta et al 1986, Zhang et al 1995, Markkula et al 1995a) and the extraocular and olfactory regions of mouse embryos (Kendall et al 1994). Also CG, present in primates and equines, is expressed in addition to the trophoblast in a variety of tumor tissues (Bellet et al 1994).…”

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confidence: 94%

Pituitary and ovarian expression of the endogenous follicle-stimulating hormone (FSH) subunit genes and an FSH β-subunit promoter-driven herpes simplex virus thymidine kinase gene in transgenic mice; specific partial ablation of FSH-producing cells by antiherpes treatment

Markkula

Kananen²,

Klemi³

et al. 1996

Journal of Endocrinology

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The ovarian expression of the endogenous follicle-stimulating hormone beta-subunit (FSH beta) and common alpha-subunit (C alpha) genes, and a herpes simplex virus thymidine kinase (tk) transgene, driven by a 2.3 kb bovine FSH beta promoter, was studied in normal and transgenic (tg) mice, tk functions not only as a neutral reporter that enables the study of the promoter function but also as an exogenously inducible toxigene. Reverse transcription-PCR followed by Southern blot hybridization with a nested probe was used to show the expression of the gene at the mRNA level. Common alpha-subunit mRNA was detected in the pituitary gland and ovaries of normal adult mice. We have previously detected endogenous FSH beta and tg tk mRNAs in the mouse pituitary, testis and ovary. In this study, the cellular localization of the corresponding proteins was visualized by immunocytochemistry. In normal mouse ovaries a positive reaction with FSH beta and C alpha antisera was seen in some of the corpora lutea and most prominently in the interstitial cells. A positive reaction with the tk antiserum was seen in the same cell types of tg mouse ovaries, but not in those of non-tg mice. Cell-ablation-inducing treatment (gancyclovir, 20 mg/kg per day, for 14 days) of tg female mice reduced pituitary FSH concentrations by 52% (P < 0.05) but did not affect pituitary LH or plasma gonadotropins compared with non-tg females treated in the same way. A longer period of cell ablation induction (acyclovir 400 mg/kg per day, for 21 days) reduced not only pituitary but also plasma FSH concentrations (55 and 57% respectively; P < 0.05) without affecting LH. This treatment also reduced ovarian weight by 38% (P < 0.01). In conclusion, our results show first that the endogenous FSH beta and C alpha proteins are produced in the mouse ovary. Hence, endogenously synthesized FSH or its subunits may have a role in the paracrine regulation of ovarian function. Secondly, the FSH beta promoter directs the expression of tg tk in the pituitary gonadotrope cells, as shown by specific but partial ablation of FSH-producing cells after induction by gancyclovir and acyclovir. In the ovary, tk protein was localized to the same compartments as the endogenous gonadotropin subunit proteins. This further confirms our finding of ovarian expression of the FSH subunit genes.

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